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Objective

Severe combined immunodeficiency (SCID) is a devastating rare disorder of immune system development. Affected infants are born without functional immune systems and die within the first year of life unless effective treatment is given. Treatment options are limited to allogeneic haematopoietic stem cell transplantation and autologous stem cell gene therapy. Over the last 15 years, gene therapy for two forms of SCID (SCID-X1 and ADA SCID) has shown significant safety and efficacy in correcting the immunodeficiency and allowing children to live normal lives. Proof of concept of gene therapy for 3 other SCID forms has also been shown by members of the proposed SCIDNET consortium and is ready for translation into clinical trials. We are therefore in a position whereby, over the next 4 years, we can offer gene therapy as a curative option for over 80% of all forms of SCID in Europe. Importantly for 1 of these conditions (ADA SCID) we will undertake clinical trials that will lead to marketing authorisation of the gene therapy product as a licensed medicine. In addition, we will investigate the future technologies that will improve the safety and efficacy of gene therapy for SCID.

Our proposal addresses an unmet clinical need in SCID, which is classified as a rare disease according to EU criteria (EC regulation No. 141/2000). The proposal also addresses the need to develop an innovative treatment such as gene therapy from early clinical trials though to a licensed medicinal product through involvement with regulatory agencies and is in keeping with the ambitions of the IRDiRC. The lead ADA SCID programme has Orphan Drug Designation and clinical trial design is assisted by engagement with the European medicines Agency. The ADA SCID trial will act as a paradigm for the development of the technologies and processes that will allow gene therapy for not only SCID, but also other bone marrow disorders, to become authorised genetic medicines in the future.

Severe combined immunodeficiency (SCID) is a devastating rare disorder of immune system development.

SCID has been at the forefront of gene therapy development and was the first condition to be effectively cured by gene therapy worldwide, through trials initiated in Paris (INSERM), London (UCL) and Milan (OSR) (all members of SCIDNET consortium). Members of the SCIDNET consortium have worked together for 15 years developing and performing the first successful clinical trials of gene therapy worldwide for two forms of SCID (SCID-X1 and ADA SCID) and also for other immunodeficiency conditions.

The challenge now is to take these trial advances and move gene therapy from the academic arena into a licensed genetic medicine that can be used as a standard treatment for patients worldwide. The SCIDNET consortium will now commercialise gene therapy for ADA SCID as a licensed medicine and this is a major objective and ambition of this proposal.

Proof of concept of gene therapy for other SCID forms (RAG1/2 and Artemis deficiency) has also been shown by members of the SCIDNET consortium and is ready for translation into clinical trials. We are therefore in a position whereby, over the next 4 years, we can offer gene therapy as a curative option for 70% of all forms of SCID in Europe. Importantly for at least 1 of these conditions (ADA SCID) we will undertake clinical trials that will lead to marketing authorisation (MA) of the gene therapy product as a licensed medicine. The ADA SCID trial will act as a paradigm for the development of the technologies and manufacturing protocols and processes that will allow gene therapy for not only SCID, but also other bone marrow disorders, to become authorised genetic medicines in the future.

SCIDNET objectives are:

1. To deliver safe and effective gene therapy as a licensed medicine for children with SCID initially within Europe and then worldwide

2. To develop the expertise and manufacturing protocols that can be used for other rare genetic diseases of the bone marrow

3. To develop the new viral and gene editing technologies that will become future gene therapy medicines, to be used routinely globally

4. To undertake studies that have Orphan Drug Designation and intellectual property protection in order to attract commercial partnership and investment

5. To engage and involve SCID families and patient support groups to help design clinical studies and to keep patient/family stakeholders informed of scientific progress

6. To engage with EU regulatory agencies in order to achieve marketing authorization across the EU for ADA SCID gene therapy by the end of the project

7. To maintain and reinforce the European leadership in developing ex vivo gene therapy in general, and gene therapy for immunodeficiencies in particular